Probiotic Analgesia for Pelvic Pain

益生菌镇痛治疗盆腔疼痛

• 批准号: 8896233
• 负责人: David J Klumpp
• 金额: $ 29.98万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-09 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8896233
• 关键词: Absence of pain sensation; Acute; Acute Pain; Afferent Neurons; Affinity; Agonist; Analgesics; Attenuated; Bacteriuria; Bladder; CCL2 gene; CD14 Antigen; Capsaicin; Cations; Chronic; Clinical Data; Clinical Research; Clinical Trials; Data; Data Set; Development; Escherichia coli; Etiology; Genetic; Goals; Health; Inflammation; Interstitial Cystitis; Lidocaine; Life; Ligands; Lipopolysaccharides; Mediating; Medicine; Modeling; Molecular; Mus; Narcotics; Neurons; Non-Steroidal Anti-Inflammatory Agents; Pain; Pain management; Pathogenesis; Pathway interactions; Patients; Pelvic Pain; Peripheral; Pharmacology; Probiotics; Protein Isoforms; Publishing; Relative (related person); Reporter; Role; Sensory; Signal Transduction; Spinal Ganglia; Staging; Structure; Symptoms; TRPV1 gene; Testing; Urinary tract infection; Uropathogenic E. coli; Virus; Work; allodynia; attenuation; base; beta-Chemokines; bladder pain; chronic pain; chronic pelvic pain; clinically relevant; innovation; intravesical; member; membrane flux; novel; pre-clinical; receptor; response; toll-like receptor 4

DESCRIPTION (provided by applicant): Pain is poorly managed in chronic pelvic pain, so new analgesic strategies are urgently needed. Our long-term goal is to harness the potential of probiotics to develop new probiotic analgesics for treating the pelvic pain of interstitial cystitis/bladder pain syndrome (IC). We previously examined the molecular basis that discriminates the symptomatic response to uropathogenic E. coli (UPEC) from the lack of response to E. coli clinically associated with asymptomatic bacteriuria (ASB). We have now accumulated compelling preliminary data demonstrating that E. coli-based probiotics alleviate both acute and chronic pelvic pain in clinically-relevant murine models that recapitulate key aspects of IC. We hypothesize that the analgesic activity of E. coli-based probiotics results from acting on three receptors involved in bladder pain signals, Toll- like receptor 4 (TLR4), transient receptor potential cation channel subfamily V member 1 (TRPV1), and chemokine C-C motif receptor 2 (CCR2). These mechanistic studies will define the analgesic ligands of probiotic E. coli and define the roles for each receptor in mediating pelvic pain in murine models of IC. These studies are highly innovative, and we are unaware of other groups studying analgesic probiotics for chronic pelvic pain. This project will thus result in a new mechanistic understanding of probiotic analgesics and provide critical pre-clinical data to drive these probiotics into clinical trials for IC.

描述（由申请人提供）：疼痛在慢性骨盆疼痛中治疗不佳，因此迫切需要新的镇痛策略。我们的长期目标是利用益生菌开发新的益生菌镇痛药来治疗间质性膀胱炎/膀胱疼痛综合征（IC）的骨盆疼痛。我们先前检查了分子基础，该分子基础与对大肠杆菌缺乏对大肠杆菌的反应有关临床上与无症状细菌尿液（ASB）的反应，从而区分了对肝癌大肠杆菌（UPEC）的有症状反应。现在，我们积累了引人注目的初步数据，表明基于大肠杆菌的益生菌可以减轻与临床相关的鼠模型的急性和慢性骨盆疼痛，这些模型概括了IC的关键方面。我们假设基于大肠杆菌的益生菌的镇痛活性是在伴有膀胱疼痛信号的三个受体上作用，Toll-Hoccoror 4（TLR4），瞬态 受体潜在阳离子通道亚家族V成员1（TRPV1）和趋化因子C-C基序受体2（CCR2）。这些机械研究将定义益生菌大肠杆菌的镇痛配体，并定义每个受体在IC鼠模型中介导骨盆疼痛中的作用。这些研究具有很高的创新性，我们不知道其他研究镇痛药的慢性骨盆疼痛的群体。因此，该项目将导致对益生菌镇痛药的新机械理解，并提供关键的临床前数据，以将这些益生菌带入IC的临床试验。